Evidence map›Paper›PMID 41316412›Full record

SynthesisStem cell research & therapy2025

Targeting cellular senescence in progenitor cells as a strategy to enhance bone regeneration by cell therapies: a systematic review of pre-clinical investigations.

Mayu Morita, Eshan B Damle, Issei Shinohara, Masatoshi Murayama, Yosuke Susuki, Qi Gao, Chao Ma, Simon Kwoon-Ho Chow, Stuart Barry Goodman

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Mayu MoritaDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0009-0003-8092-0762
Eshan B DamleDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.
Issei ShinoharaDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.
Masatoshi MurayamaDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.
Yosuke SusukiDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.
Qi GaoDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.
Chao MaDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.
Simon Kwoon-Ho ChowDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA.
Stuart Barry GoodmanDepartment of Orthopaedic Surgery, School of Medicine, Stanford University, Palo Alto, CA, USA. goodbone@stanford.edu.

Funding

Japan Society for the Promotion of Science (JPSP) KAKENHI 23K16132Robert L. and Mary Ellenburg Professorship of Surgery Robert L. and Mary Ellenburg Professorship of Surgery
6 · The paper itself

Abstract

backgroundWith the global population aging, optimizing bone regeneration is becoming increasingly important for enhancing the quality of life among elderly individuals. Progenitor cell-based therapies, such as mesenchymal stromal cells and induced pluripotent stem cells for bone regeneration have shown challenges due to cellular senescence and the control of the differentiation processes remain significant hurdles. In particular, elevated expression of senescence markers may play a pivotal role in limiting bone regeneration. This systematic review examines how these senescence markers influence the efficacy of progenitor cell therapies and whether targeting them could improve outcomes.

methodsWe conducted a systematic literature review following the PRISMA guidelines, using the PubMed, Web of Science, Embase and Scopus with the algorithm of "bone regeneration AND senescence AND marker". Data synthesis focused on human cell sources and specifically examined senescence markers related to bone regeneration.

resultsStudies using human cells were discussed in 101 papers. Based on our inclusion and exclusion criteria, 13 papers remained for our review on senescence markers in human cells within the context of bone regeneration and senescence, with and without interventional strategies. More than half of the cell sources in current aging-related studies are derived from bone marrow. Markers of aging relevant to bone regeneration include changes in cell size and morphology, increased levels of β-galactosidase (β-Gal) and Reactive Oxygen Species (ROS), and the presence of a senescence-associated secretory phenotype (SASP). Additionally, distinct senescence markers such as p16Ink4a, p21, and p53, and mitochondrial dysfunction were associated with reduced osteogenic potential and impaired regenerative capacity.

conclusionBone marrow is the most common source of cells for studies of senescence. Cellular senescence characterized by elevated expression of specific markers was consistently shown to be negatively associated with osteogenic capacity and regenerative outcomes. The most common strategies to rejuvenate senescent cells include targeting of senescence markers and oxidative stress. Among these, modulation of p53, p21, and p16 signaling pathways has been highlighted as a potential therapeutic approach for mitigating cell senescence in bone-related conditions.

Indexed as

Bone RegenerationCell- and Tissue-Based TherapyCellular SenescenceStem CellsAnimalsCell DifferentiationHumansMesenchymal Stem CellsOsteogenesisBone regenerationCellular senescencep16p21p53ROSSenescence marker

Identifiers

PMID41316412
PMCPMC12664153

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.